168 research outputs found
Existing evidence on the use of participatory scenarios in ecological restoration: a systematic map
Background and context: The scale of land degradation worldwide has led to nearly one billion hectares committed to restoration globally. However, achieving such restoration targets will necessitate complex trade-offs against limited time, competing knowledge, costs, resources and varying stakeholder and societal preferences. Participatory scenarios allow a way to identify collaborative solutions for restoration planning and implementation best suited for the local cultures and societies they are tied to. They can be used to navigate uncertainties surrounding future trajectories of restored areas by evaluating trade-offs in outcomes. This research aims to systematically map the evidence on the use of participatory scenarios in restoration planning. We use the following research question: What evidence exists on the use of participatory scenarios in ecological restoration? This is answered by examining the characteristics of the evidence base, types of study design, types of outcomes, trade-offs in outcomes, and the role of participants. Methods: A comprehensive and reproducible search strategy was followed using bibliographic databases, web-based searches, and targeted searching. Search results underwent a two-step screening process according to eligibility criteria. Metadata on key areas of interest were extracted from included texts and were narratively synthesised alongside data visualisations to answer the research questions. Review findings:18,612 records were initially identified, and 106 articles were included in the final map. Most studies were conducted in Europe and North America, focusing on restoring agricultural land or forests. Most texts used mixed methods and explored multiple outcome types, but environmental outcomes were the most assessed. Within environmental outcomes, indicators for ecological function were assessed more frequently than structural or compositional indicators. The most common reason for choosing outcomes and indicators was stakeholder interest. Trade-offs in social, ecological, and economic outcomes were mainly examined across space using mapping techniques, while far fewer studies looked at trade-offs across stakeholders and time. Participants were mostly included in the scenario creation step and were usually chosen purposefully by the research team. Conclusions: It is difficult to understand how useful scenarios are for restoration planning because few texts reported how scenarios fed into the process. Despite this, the range of outcomes used and different method types adopted suggests participatory scenarios allow for integrating different knowledge and approaches, alongside facilitating the use of qualitative or semi-quantitative data when this is more appropriate or quantitative data is not widely available. To better use participatory scenarios as a tool for ecological restoration planning, decision-makers can push for greater levels and definitions of participation from the offset of restoration projects with specified, regular, and structured communication and participation channels. We also recommend more systematic methods of participant selection, such as stakeholder analysis. Further research is needed to understand the effectiveness of participatory scenarios in restoration planning and whether the participation of stakeholders was successful in meeting objectives. To improve the evidence base, future studies should clearly evaluate their effectiveness in the restoration planning process and their success in meeting their participatory objectives
Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution
APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast DCIS, and in pre-invasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx pre-invasive to invasive NSCLC lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models, revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in pre-invasive disease, providing fuel for selection early in cancer evolution
Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition
Checkpoint inhibitors (CPIs) augment adaptive immunity. Systematic pan-tumor analyses may reveal the relative importance of tumor-cell-intrinsic and microenvironmental features underpinning CPI sensitization. Here, we collated whole-exome and transcriptomic data for >1,000 CPI-treated patients across seven tumor types, utilizing standardized bioinformatics workflows and clinical outcome criteria to validate multivariable predictors of CPI sensitization. Clonal tumor mutation burden (TMB) was the strongest predictor of CPI response, followed by total TMB and CXCL9 expression. Subclonal TMB, somatic copy alteration burden, and histocompatibility leukocyte antigen (HLA) evolutionary divergence failed to attain pan-cancer significance. Dinucleotide variants were identified as a source of immunogenic epitopes associated with radical amino acid substitutions and enhanced peptide hydrophobicity/immunogenicity. Copy-number analysis revealed two additional determinants of CPI outcome supported by prior functional evidence: 9q34 (TRAF2) loss associated with response and CCND1 amplification associated with resistance. Finally, single-cell RNA sequencing (RNA-seq) of clonal neoantigen-reactive CD8 tumor-infiltrating lymphocytes (TILs), combined with bulk RNA-seq analysis of CPI-responding tumors, identified CCR5 and CXCL13 as T-cell-intrinsic markers of CPI sensitivity
Chief examiners as Prophet and Priest: relations between examination boards and school subjects, and possible implications for knowledge
Evidence from an ethnographic study of three secondary school geography departments in England is drawn on to describe aspects of the relationships between examination boards and school subjects. This paper focuses on one department, in ‘Town Comprehensive’, and the argument is illustrated through a discussion of observed lessons with a teacher in this department. Ofqual (Office of Qualifications and Examinations Regulation) have recently announced that examination boards may continue to endorse commercially available teaching resources. The argument presented in this paper extends possible areas of ‘risk’ identified beyond those they currently consider. Specifically, it is argued that chief examiners play multiple roles in the recontextualisation of knowledge, holding substantial power over school subjects. The strong role of accreditation as a rationale is argued to restrict knowledge taught in school geography to horizontal discourses, limiting students’ access to powerful knowledge
Peritoneal changes due to laparoscopic surgery
Item does not contain fulltextBACKGROUND: Laparoscopic surgery has been incorporated into common surgical practice. The peritoneum is an organ with various biologic functions that may be affected in different ways by laparoscopic and open techniques. Clinically, these alterations may be important in issues such as peritoneal metastasis and adhesion formation. METHODS: A literature search using the Pubmed and Cochrane databases identified articles focusing on the key issues of laparoscopy, peritoneum, inflammation, morphology, immunology, and fibrinolysis. Results : Laparoscopic surgery induces alterations in the peritoneal integrity and causes local acidosis, probably due to peritoneal hypoxia. The local immune system and inflammation are modulated by a pneumoperitoneum. Additionally, the peritoneal plasmin system is inhibited, leading to peritoneal hypofibrinolysis. CONCLUSION: Similar to open surgery, laparoscopic surgery affects both the integrity and biology of the peritoneum. These observations may have implications for various clinical conditions.1 januari 201
Global economic burden of unmet surgical need for appendicitis
Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US 73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was 75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially
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